IV immunoglobulin does not reverse established weakness in MS: A double-blind, placebo-controlled trial

John H. Noseworthy, P. C. O'Brien, Brian G Weinshenker, J. A. Weis, T. M. Petterson, Bradley J Erickson, Anthony John Windebank, J. P. Whisnant, K. A. Stolp-Smith, C. M. Harper, Phillip Anson Low, L. J. Romme, M. Johnson, K. N. An, M. Rodriguez

Research output: Contribution to journalArticle

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Abstract

Background: Immunoglobulin (Ig) administration induces remyelination in the Theiler's virus model of MS. Methods: A randomized, double-blinded, placebo-controlled trial of IV immunoglobulin (IVIg) was performed in patients with MS who had persistent muscle weakness that had been stable for between 4 and 18 months to determine whether this would improve muscle strength (primary outcome: isometric muscle strength). Patients received either IVIg (0.4 g/kg) or placebo daily for 5 days, then single infusions every 2 weeks for 3 months (total, 11 infusions). Muscle groups identified by clinical measures to have unchanging significant weakness were the major targets for therapeutic response (targeted neurologic deficit [TND]). Results: IVIg was well tolerated. An interim analysis after 67 patients were enrolled indicated no difference in the degree of change in strength between treatment groups in either the TND or non-TND muscle groups at 6 months, and the trial was terminated. There was no apparent benefit in relapse behavior or impairment measures during the 6-month observation period. Nor was there apparent benefit in either patients who remained clinically stable or in those with evidence of disease activity. Patients with active MS during the trial worsened in both TND and non-TND muscle groups. This worsening was seen regardless of whether the clinical manifestations of disease activity involved the TND muscle groups. Conclusions: IVIg does not reverse established weakness in MS. Measurements of isometric muscle strength were reliable (reproducible) indices of strength and may be sensitive, objective methods to document functional changes in impairment in future MS trials.

Original languageEnglish (US)
Pages (from-to)1135-1143
Number of pages9
JournalNeurology
Volume55
Issue number8
StatePublished - Oct 24 2000

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Intravenous Immunoglobulins
Neurologic Manifestations
Placebos
Muscle Strength
Muscles
Theilovirus
Muscle Weakness
Immunoglobulins
Observation
Recurrence
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Noseworthy, J. H., O'Brien, P. C., Weinshenker, B. G., Weis, J. A., Petterson, T. M., Erickson, B. J., ... Rodriguez, M. (2000). IV immunoglobulin does not reverse established weakness in MS: A double-blind, placebo-controlled trial. Neurology, 55(8), 1135-1143.

IV immunoglobulin does not reverse established weakness in MS : A double-blind, placebo-controlled trial. / Noseworthy, John H.; O'Brien, P. C.; Weinshenker, Brian G; Weis, J. A.; Petterson, T. M.; Erickson, Bradley J; Windebank, Anthony John; Whisnant, J. P.; Stolp-Smith, K. A.; Harper, C. M.; Low, Phillip Anson; Romme, L. J.; Johnson, M.; An, K. N.; Rodriguez, M.

In: Neurology, Vol. 55, No. 8, 24.10.2000, p. 1135-1143.

Research output: Contribution to journalArticle

Noseworthy, JH, O'Brien, PC, Weinshenker, BG, Weis, JA, Petterson, TM, Erickson, BJ, Windebank, AJ, Whisnant, JP, Stolp-Smith, KA, Harper, CM, Low, PA, Romme, LJ, Johnson, M, An, KN & Rodriguez, M 2000, 'IV immunoglobulin does not reverse established weakness in MS: A double-blind, placebo-controlled trial', Neurology, vol. 55, no. 8, pp. 1135-1143.
Noseworthy, John H. ; O'Brien, P. C. ; Weinshenker, Brian G ; Weis, J. A. ; Petterson, T. M. ; Erickson, Bradley J ; Windebank, Anthony John ; Whisnant, J. P. ; Stolp-Smith, K. A. ; Harper, C. M. ; Low, Phillip Anson ; Romme, L. J. ; Johnson, M. ; An, K. N. ; Rodriguez, M. / IV immunoglobulin does not reverse established weakness in MS : A double-blind, placebo-controlled trial. In: Neurology. 2000 ; Vol. 55, No. 8. pp. 1135-1143.
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abstract = "Background: Immunoglobulin (Ig) administration induces remyelination in the Theiler's virus model of MS. Methods: A randomized, double-blinded, placebo-controlled trial of IV immunoglobulin (IVIg) was performed in patients with MS who had persistent muscle weakness that had been stable for between 4 and 18 months to determine whether this would improve muscle strength (primary outcome: isometric muscle strength). Patients received either IVIg (0.4 g/kg) or placebo daily for 5 days, then single infusions every 2 weeks for 3 months (total, 11 infusions). Muscle groups identified by clinical measures to have unchanging significant weakness were the major targets for therapeutic response (targeted neurologic deficit [TND]). Results: IVIg was well tolerated. An interim analysis after 67 patients were enrolled indicated no difference in the degree of change in strength between treatment groups in either the TND or non-TND muscle groups at 6 months, and the trial was terminated. There was no apparent benefit in relapse behavior or impairment measures during the 6-month observation period. Nor was there apparent benefit in either patients who remained clinically stable or in those with evidence of disease activity. Patients with active MS during the trial worsened in both TND and non-TND muscle groups. This worsening was seen regardless of whether the clinical manifestations of disease activity involved the TND muscle groups. Conclusions: IVIg does not reverse established weakness in MS. Measurements of isometric muscle strength were reliable (reproducible) indices of strength and may be sensitive, objective methods to document functional changes in impairment in future MS trials.",
author = "Noseworthy, {John H.} and O'Brien, {P. C.} and Weinshenker, {Brian G} and Weis, {J. A.} and Petterson, {T. M.} and Erickson, {Bradley J} and Windebank, {Anthony John} and Whisnant, {J. P.} and Stolp-Smith, {K. A.} and Harper, {C. M.} and Low, {Phillip Anson} and Romme, {L. J.} and M. Johnson and An, {K. N.} and M. Rodriguez",
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T1 - IV immunoglobulin does not reverse established weakness in MS

T2 - A double-blind, placebo-controlled trial

AU - Noseworthy, John H.

AU - O'Brien, P. C.

AU - Weinshenker, Brian G

AU - Weis, J. A.

AU - Petterson, T. M.

AU - Erickson, Bradley J

AU - Windebank, Anthony John

AU - Whisnant, J. P.

AU - Stolp-Smith, K. A.

AU - Harper, C. M.

AU - Low, Phillip Anson

AU - Romme, L. J.

AU - Johnson, M.

AU - An, K. N.

AU - Rodriguez, M.

PY - 2000/10/24

Y1 - 2000/10/24

N2 - Background: Immunoglobulin (Ig) administration induces remyelination in the Theiler's virus model of MS. Methods: A randomized, double-blinded, placebo-controlled trial of IV immunoglobulin (IVIg) was performed in patients with MS who had persistent muscle weakness that had been stable for between 4 and 18 months to determine whether this would improve muscle strength (primary outcome: isometric muscle strength). Patients received either IVIg (0.4 g/kg) or placebo daily for 5 days, then single infusions every 2 weeks for 3 months (total, 11 infusions). Muscle groups identified by clinical measures to have unchanging significant weakness were the major targets for therapeutic response (targeted neurologic deficit [TND]). Results: IVIg was well tolerated. An interim analysis after 67 patients were enrolled indicated no difference in the degree of change in strength between treatment groups in either the TND or non-TND muscle groups at 6 months, and the trial was terminated. There was no apparent benefit in relapse behavior or impairment measures during the 6-month observation period. Nor was there apparent benefit in either patients who remained clinically stable or in those with evidence of disease activity. Patients with active MS during the trial worsened in both TND and non-TND muscle groups. This worsening was seen regardless of whether the clinical manifestations of disease activity involved the TND muscle groups. Conclusions: IVIg does not reverse established weakness in MS. Measurements of isometric muscle strength were reliable (reproducible) indices of strength and may be sensitive, objective methods to document functional changes in impairment in future MS trials.

AB - Background: Immunoglobulin (Ig) administration induces remyelination in the Theiler's virus model of MS. Methods: A randomized, double-blinded, placebo-controlled trial of IV immunoglobulin (IVIg) was performed in patients with MS who had persistent muscle weakness that had been stable for between 4 and 18 months to determine whether this would improve muscle strength (primary outcome: isometric muscle strength). Patients received either IVIg (0.4 g/kg) or placebo daily for 5 days, then single infusions every 2 weeks for 3 months (total, 11 infusions). Muscle groups identified by clinical measures to have unchanging significant weakness were the major targets for therapeutic response (targeted neurologic deficit [TND]). Results: IVIg was well tolerated. An interim analysis after 67 patients were enrolled indicated no difference in the degree of change in strength between treatment groups in either the TND or non-TND muscle groups at 6 months, and the trial was terminated. There was no apparent benefit in relapse behavior or impairment measures during the 6-month observation period. Nor was there apparent benefit in either patients who remained clinically stable or in those with evidence of disease activity. Patients with active MS during the trial worsened in both TND and non-TND muscle groups. This worsening was seen regardless of whether the clinical manifestations of disease activity involved the TND muscle groups. Conclusions: IVIg does not reverse established weakness in MS. Measurements of isometric muscle strength were reliable (reproducible) indices of strength and may be sensitive, objective methods to document functional changes in impairment in future MS trials.

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